Comparative studies of extraction chromatography and electro-amalgamation separation to produce no-carrier added 177Lu by Tehran research reactor

Document Type : Original Article


1 Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran, Iran

2 Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, Tehran, Iran


Introduction:Owing to its favorable radionuclidic characteristics, such as tl/2 = 6.73 day and Eβ (max) = 497 keV and ease of its large-scale production using medium flux research reactors, lutetium-177 (177Lu) is an attractive radionuclide for various therapeutic applications. No carrier added (NCA) 177Lu was obtained by thermal neutron bombardment (4×1013n/cm2.s) of 176Yb target through 176Yb(n, γ)177Yb        177Lu process have the advantage of preparing radiopharmaceuticals with high specific activity. So the existence of an effective Lu/Yb separation method is critical.
Methods: Many researchers illustrated no-carrier added 177Lu production. However, the present study is based on comparison between two potential separation methods, namely extraction chromatography and electro-amalgamation separation with respect to separation yield and radiochemical characteristics.
Results: The no carrier added 177Lu separated from 176Yb target by two extraction chromatography and electro-amalgamation separation methods. The effective parameters on separation Lu/Yb were investigated in two procedures. The 177Lu production yield by extraction chromatography and electro-amalgamation procedures were 82% and 88.83% respectively. The no carrier added 177Lu was obtained with radionuclidic purity of 99.99%   in two separation methods.

Conclusion: Although both separation methods have exhibited promising feature, the study reveals that electro-amalgamation separation offers the advantages of higher yield of 177Lu, simplicity and easier to operate for large amount of target and less overall processing time.


Main Subjects

  1. Koppe MJ, Bleichrodt RP, Soede AC, Verhofstad AA, Goldenberg DM, Oyen WJ, Boerman OC. Biodistribution and therapeutic efficacy of (125/131)I-, (186)Re-, (88/90)Y-, or (177)Lu-labeled monoclonal antibody MN-14 to carcinoembryonic antigen in mice with small peritoneal metastases of colorectal origin. J Nucl Med. 2004 Jul;45(7):1224-32.
  2. Brouwers AH, van Eerd JE, Frielink C, Oosterwijk E, Oyen WJ, Corstens FH, Boerman OC. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re. J Nucl Med. 2004 Feb;45(2):327-37.
  3. Dash A, Pillai MR, Knapp FF Jr. Production of (177)Lu for Targeted Radionuclide Therapy: Available Options. Nucl Med Mol Imaging. 2015 Jun;49(2):85-107.
  4. Banerjee S, Das T, Chakraborty S, Venkatesh M. Emergence and present status of Lu-177 in targeted radiotherapy: The Indian scenario. Radiochimica Acta. 2012;100(2):115-126.
  5. Pommé S, Paepen J, Altzitzoglou T, Van Ammel R, Yeltepe E. Measurement of the 177Lu half-life. Appl Radiat Isot. 2011 Sep;69(9):1267-73.
  6. Firestone R, Shirely VS, eds. Table of isotopes. 8th ed. New York: John Wiely and Sons; 1996.
  7. Das T, Chakraborty S, Unni PR, Banerjee S, Samuel G, Sarma HD, Venkatesh M, Pillai MR. 177Lu-labeled cyclic polyaminophosphonates as potential agents for bone pain palliation. Appl Radiat Isot. 2002 Aug;57(2):177-84. 
  8. Lashko AP, Lashko TN. The study of 177mLu decay. Probl Atom Sci Tech. 2013;60:129-135.
  9. Dvorkov Z: Production and chemical processing of 177Lu for nuclear medicine at the Munich research reactor FRM-II. Thesis in Institut fur Radiochemie der Technischen Universitat Munchen; 2007.
  10. Mirzadeh S, Du M, Beets AL, Knapp Jr FF. Method for preparing high specific activity 177Lu. 2004; US Patent, US 6716353 B1.
  11. Haettner E, Iwase H, Schardt D. Experimental fragmentation studies with 12C therapy beams. Radiat Prot Dosimetry. 2006;122(1-4):485-7.
  12. Choppin GR, Silva RJ. Separation of the lanthanides by ion exchange with alpha-hydroxyisobutyric acid. J Inorg Nucl Chem. 1956;3:153-154.
  13. Marhol M. Ion exchangers in analytical chemistry: Their properties and use in inorganic chemistry. Compr Anal Chem. 1982;14:2-585.
  14. Starý J. Separation of transplutonium elements. Talanta. 1966 Mar;13(3):421-437.
  15. Denzler FO, Lebedev NA, Novgorodov AF, Rosch F, Qaim SM. Production and radiochemical separation of 147Gd. Appl Radiat Isotopes. 1997;48(3):319–326.
  16. Marx S, Harfensteller M, Zhernosekov K, Nikula T. Method of manufacturing non carrier added high purity 177Lu compounds as well as non-carrier added 177Lu compounds. United States patent application publication, 2014; US 2014/0294700A1.
  17. Balasubramanian PS. Separation of carrier-free lutetium-177 from neutron irradiated natural ytterbium target. J Radioanal Nucl Chem. 1994;185:305-10.
  18. Hashimoto K, Matsuoka H, Uchida S. Production of no-carrier-added 177Lu via the 176Yb (n, γ) 177Yb→177Lu process. J Radioanal Nucl Chem. 2003;255:575-79.
  19. Lahiri S, Nayak D, Nandy M, Das NR. Separation of carrier free lutetium produced in proton activated ytterbium with HDEHP. Appl Radiat Isotopes. 1998;49(8):911-13.
  20. Kumrić K, Trtić-Petrović T, Koumarianou E, Archimandritis S, Čomor JJ.   Supported liquid membrane extraction of 177Lu (III) with DEHPA and its application for purification of 177Lu-DOTAlanreotide. Sep Purif Technol. 2006;51(3):310-17.
  21. Watanabe S, Hashimoto K, Watanabe S, Iida Y, Hanaoka H, Endo K, Ishioka NS.  Production of highly purified no-carrier-added 177Lu for radioimmunotherapy. J Radioanal Nucl Chem. 2015;303:935-40.
  22. Knapp Jr FR, Mirzadeh S, Beets AL, Du M. Production of therapeutic radioisotopes in the ORNL High Flux Isotope Reactor (HFIR) for applications in nuclear medicine, oncology and interventional cardiology. J Radioanal Nucl Chem. 2005;263:503-9.
  23. Horwitz EP, McAlister DR, Bond AH, Barrans RE, Williamson JM. A process for the separation of 177Lu from neutron irradiated 176Yb targets. Appl Radiat Isotopes. 2005;63:23-36.
  24.  So LV, Morcos N, Zaw M, Pellegrini P, Greguric I. Alternative chromatographic processes for no-carrier added 177Lu radioisotope separation. Part I. Multi-column chromatographic process for clinically applicable. J Radioanal Nucl Chem. 2008;277:663-73.
  25. So LV, Morcos N, Zaw M, Pellegrini P, Greguric I, Nevissi A. Alternative chromatographic processes for no-carrier added 177Lu radioisotope separation. Part II. The conventional column chromatographic separation combined with HPLC for high purity. J Radioanal Nucl Chem. 2008;277:675-83.
  26. Monroy-Guzman F, Barreiro FJ, Salinas EJ, Treviño ALV. Radiolanthanides device production. World J Nucl Sci Technol. 2015;5:111-19.
  27. Lebedev NA, Novgorodov AF, Misiak R, Brockmann J, Rösch F. Radiochemical separation of no-carrier-added 177Lu as produced via the 176Yb (n, γ) 177Yb→177Lu process. . Appl Radiat Isotopes. 2000;53:421-25.
  28. Bilewicz A, Żuchowska K, Bartoś B. Separation of Yb as YbSO4 from 176Yb target for production of 177Lu via the 176Yb (n, γ) 177Yb→177Lu process. J Radioanal Nucl Chem. 2009;280:167-69.
  29. Chakravarty R, Das T, Dash A, Venkatesh M. An electro-amalgamation approach to isolate no-carrier-added 177Lu from neutron irradiated Yb for biomedical applications. Nucl Med Biol. 2010 Oct;37(7):811-20.
  30. Cieszykowska I, Zóltowska M, Mielcarski M. Separation of Ytterbium from 177Lu/Yb mixture by electrolytic reduction and amalgamation. SOP Trans Appl Chem. 2014;1(2):6-13.